Cytotoxic T lymphocyte antigen-4 (“CTLA-4”) is a member of the immunoglobulin (“Ig”) superfamily of proteins. CTLA-4 acts to down regulate T-cell activation and maintain immunologic homeostasis. Blockade of CTLA-4 (e.g., by use of CTLA-4 antibodies) has been shown in animal models to improve the effectiveness of cancer immunotherapy.
Antibodies that bind to and inhibit the activity of CTLA-4 have been reported in the literature. For example, U.S. Pat. No. 6,682,736 assigned to Pfizer, Inc. and Abgenix, Inc., reports several human monoclonal antibodies to CTLA-4, including a CTLA-4 antibody having the heavy and light chain amino acid sequences of antibody 11.2.1, now known as Ticilimumab™. A hybridoma cell line producing antibody 11.2.1 was deposited under ATCC Accession No. PTA-5169. U.S. Pat. No. 5,977,318 assigned to Bristol-Myers Squibb Company, reports another monoclonal antibody, which recognizes and binds the extracellular domain of CTLA-4, thereby preventing the binding of CTLA-4 to the B7 antigen. U.S. Published Application No. 20050201994 assigned to Medarex, Inc. reports several human sequence antibodies to CTLA-4, including one now referred to as Ipilimumab™.
One possible mode of administering such CTLA-4 antibodies is by parenteral administration. For example, U.S. Pat. No. 6,682,736 reports an anti-CTLA-4 antibody intravenous formulation that is a sterile liquid solution containing anti-CTLA-4 antibodies, 20 mM sodium acetate, 0.2 mg/ml polysorbate 80, and 140 mM sodium chloride at pH 5.5.
Like other protein formulations, CTLA-4 antibody formulations are subject to the same concerns regarding chemical and physical degradation of the antibody in the formulation over time. In general, CTLA-4 antibody formulations should exhibit acceptable chemical and physical stability under the expected range of storage and use conditions, i.e., the CTLA-4 antibody formulation should have a sufficient shelf life yet remain biologically active. Given the time and resources necessary to produce a CTLA-4 antibody product, formulations that reduce product loss are desirable. Accordingly, the present application discloses novel CTLA-4 antibody formulations that exhibit improved chemical and/or physical stability relative to CTLA-4 antibody formulations previously disclosed in the literature.